丝氨酸蛋白酶和基质金属蛋白酶系统在人类关节软骨破坏中的意义。

Significance of serine proteinase and matrix metalloproteinase systems in the destruction of human articular cartilage.

Kikuchi H, Shimada W, Nonaka T, Ueshima S, Tanaka S

Department of Orthopaedic Surgery, Kinki University, School of Medicine, Osakasayama, Japan.

Clin Exp Pharmacol Physiol. 1996 Oct-Nov;23(10-11):885-9. doi: 10.1111/j.1440-1681.1996.tb01138.x.

Abstract

During the destruction of articular cartilage, fibrinolytic enzymes and matrix metalloproteinases (MMP) may contribute to the related pathology. The activities, antigens and messenger RNA (mRNA) levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in articular cartilage were measured in patients with no history of joint diseases (control), those with osteoarthritis (OA) classified into osteophyte-formed site (OS) and weight-bearing site (WS), and in patients with rheumatoid arthritis (RA). 2. The uPA content was higher in WS and RA compared to normal. The PAI-1 content was higher in OS and RA compared to normal. Weight-bearing site patients expressed a high uPA mRNA level but a low PAI-1 mRNA level. Osteophyte-formed site patients expressed a low uPA mRNA level but a high PAI-1 mRNA level. 3. The levels of the MMP and mRNA of tissue inhibitors of metalloproteinases (TIMP) were measured in WS, OS, and RA. In WS, the levels of MMP were high and levels of TIMP mRNA expression low. In OS, the levels of TIMP were high and levels of MMP mRNA were low. In RA, the levels of MMP and TIMP mRNA were high. 4. These findings suggest that regulation of fibrinolysis may play an important role in the matrix of articular cartilage with arthropathy.

摘要

在关节软骨破坏过程中，纤溶酶和基质金属蛋白酶（MMP）可能与相关病理过程有关。对无关节疾病史的患者（对照组）、骨关节炎（OA）患者（分为骨赘形成部位组（OS）和负重部位组（WS））以及类风湿关节炎（RA）患者的关节软骨中尿激酶型纤溶酶原激活剂（uPA）和纤溶酶原激活剂抑制剂-1（PAI-1）的活性、抗原及信使核糖核酸（mRNA）水平进行了测定。2. 与正常情况相比，WS组和RA组的uPA含量更高。与正常情况相比，OS组和RA组的PAI-1含量更高。负重部位组患者的uPA mRNA水平较高，但PAI-1 mRNA水平较低。骨赘形成部位组患者的uPA mRNA水平较低，但PAI-1 mRNA水平较高。3. 对WS组、OS组和RA组的MMP水平以及金属蛋白酶组织抑制剂（TIMP）的mRNA水平进行了测定。在WS组中，MMP水平较高，TIMP mRNA表达水平较低。在OS组中，TIMP水平较高，MMP mRNA水平较低。在RA组中，MMP和TIMP mRNA水平均较高。4. 这些发现表明，纤维蛋白溶解的调节可能在关节病关节软骨基质中起重要作用。